This invention relates to mass spectrometers, and more particularly relates to multiple stage multipole spectrometers and a technique for removing a background spectrum.
Presently, mass spectrometers, particularly triple quadrupole mass spectrometers, are often used to analyze fairly complex reaction or fragmentation schemes. Thus, it is often desired to select a parent ion, fragment the parent ion to generate daughter ions, and subsequently fragment the daughter ions to create further fragment or granddaughter ions. Typically, only a single stage of fragmentation can be performed in a continuous beam triple quadrupole mass spectrometer. Subsequent stages of fragmentation are performed using alternative techniques such as radial excitation, a method common in the field of ion traps. Here the secular frequency xcfx89 of the parent ion is excited using a suitable excitation field such as an auxiliary dipole or quadrupole field. The degree of excitation depends on the amplitude of the auxiliary field; at low voltages, typically less than several volts, the ion is excited, but not ejected. At high amplitudes, typically several volts, the ion is ejected from the rod array and strikes the rods. It is well known that the secular frequency xcfx89 is approximately given by the equation xcfx89=(a+q2/2)xcexa9/2, for qxe2x89xa60.4, where a and q are the stability parameters arising from the Matthieu equation and xcexa9 is the RF drive frequency. Thus, the excitation field is tuned to a frequency for exciting the parent ion, at an amplitude that yields good fragmentation without ejecting the ion. A detector or mass spectrometer stage is then used to determine the amount of granddaughter or secondary fragmentation ions present, which in turn can be used to determine the structure and composition of the original starting material. The problem with such a scheme is that there are numerous paths by which different components might be present in the final ion sample that is measured. This in turn creates a requirement to track the background spectrum, so as to determine the true spectra created by the secondary fragmentation of a selected primary fragment or daughter ions. For example, some of the ions present in the final sample may not have been created by fragmentation of the selected daughter ion, but rather, may have resulted from the initial fragmentation.
Techniques have been proposed in the art for software subtraction methods, for example by simply subtracting the background from the signal on a point by point basis. These are best suited for cases where the signal of interest is high relative to a low background component, e.g. S/N greater than  greater than 1. In contrast, in the sort of scheme outlined above, i.e. continuous flow, multiple stage fragmentation, it is likely for the background signal to be as large or much larger than the signal of interest, S/N less than 1. It is very difficult to resolve this kind of situation downstream of a mass spectrometer.
Further known techniques include using broadband excitation which remove all ions within a specific mass range. Use of a broadband excitation in a continuous flow device is feasible but it requires higher power and implementation is costly and difficult.
The use of resonant excitation to selectively remove specific m/z ions is well known in the field. In a paper entitled xe2x80x9cA Technique for Mass Selective Ion Rejection in a Quadrupole Reaction Chamberxe2x80x9d by J. Throck Watson et al, there is a proposal to selectively reject from the r.f.-only collision cell of a tandem quadrupole mass spectrometer certain ions, with a view to enhancing analysis of different reactional fragmentation schemes. (International Journal of Mass Spectrometry and Ion Processes, 93 (1989) 225-235). A further paper entitled xe2x80x9cA Notch Rejection Quadrupole Mass Filterxe2x80x9d by Philip E Miller et al (International Journal of Mass Spectrometry and Ion Processes, 96 (1990) 17-26) discloses a technique in which a quadrupole is tuned to permit a wide range of masses to be transmitted, and to have a notch which selectively rejects one or more masses. In both these papers, there is no suggestion that the mass selected for rejection be tuned or linked in any way with the later stage in the spectrometer.
Accordingly, in a multiple stage mass spectrometer performing multiple stages of mass spectrometry (MS), particularly where there are multiple fragmentation stages, it is highly desirable to provide some technique for removing the background. More particularly, it is desirable to provide a technique for removing the background in real time or xe2x80x9con the flyxe2x80x9d rather than relying on some later processing technique to remove the background.
In accordance with the present invention, there is provided a mass spectrometer apparatus comprising;
a first mass analyzer stage for selecting ions having a particular mass-to-charge ratio;
a fragmentation stage downstream from the first mass analysis stage for causing fragmentation of ions;
a second mass analysis stage downstream from the fragmentation stage for selecting ions of a particular mass-to-charge ratio and rejecting other ions;
and a synchronization unit connected between the first and second mass analysis stages, whereby ions excited and removed in the first mass analysis stage have the same mass-to-charge ratio as the ions selected by the second mass analysis stage, whereby ions detected by the detector are ions selected by the second mass analysis stage and generated by fragmentation in the fragmentation stage.
Another aspect of the present invention provides a method of analyzing an ion stream, the method comprising:
(1) selecting ions having a particular mass-to-charge ratio from the ion stream;
(2) causing fragmentation of the remaining ions to generate fragment ions;
(3) subsequently selecting ions having a desired mass-to-charge ratio for detection, and detecting the quantity of ions having the desired mass-to-charge ratio; and
(4) synchronizing the selected mass-to-charge ratio in step (1) with the desired mass-to-charge ratio in step (3), whereby detected ions having the desired mass-to-charge ratio will have been generated by fragmentation in step (2).
Both the apparatus and method of the present invention can be applied to a scheme where two or more fragmentation stages take place. In such a situation, there would be provided upstream of the first mass analysis stage, an initial mass analysis or spectrometer stage, for selecting a parent ion, and a further fragmentation stages, for causing fragmentation of the parent ion, to generate daughter ions. These daughter ions would then pass into the first mass analysis stage, for selection, and the fragmentation stage would then generate granddaughter ions from the daughter ions, etc.
Mass analysis and fragmentation can be carried out in any suitable apparatus. However, it is preferred for these steps to be carried out in a quadrupole mass spectrometer. Such a spectrometer can provide a plurality of stages, each comprising a quadrupole rod set aligned with adjacent stages, and configured to carry out the various steps in mass analysis, fragmentation, etc.